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Trial record 65 of 248 for:    test AND provocation

Amyloidopathy, Choinopathy, Dopamine Responsiveness and Freezing of Gait in PD

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ClinicalTrials.gov Identifier: NCT03647137
Recruitment Status : Recruiting
First Posted : August 27, 2018
Last Update Posted : February 22, 2019
Sponsor:
Collaborator:
University of Michigan
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing PD is associated with disabling axial motor complications, such as freezing of gait (FoG), with decreased or even refractory dopamine responsiveness in over 50% of patients. The management of dopamine resistant gait problems represents the most important unmet need in PD. This study will related detailed motor testing to brain PET imaging to see if certain molecules (or lack thereof) involved with neurologic transmission in the brain are involved with FoG.

Condition or disease Intervention/treatment
Parkinson's Disease Other: Detailed motor testing, including FoG, in PD subjects

Detailed Description:
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing PD is associated with disabling axial motor complications, such as freezing of gait (FoG), with decreased or even refractory dopamine responsiveness in over 50% of patients. The management of dopamine resistant gait problems represents the most important unmet need in PD. At present, there is no biomarker of FoG in patients with PD as there is a lack of mechanistic understanding of dopamine nonresponsiveness of FoG. The investigators have previously identified cholinergic denervation as a prominent factor related to both falls and gait slowing in PD. The investigators recently identified that cortical -amyloid deposition not only associates with cognitive decline but also with postural instability and gait difficulties in PD. In this proposal, the investigators present preliminary data suggesting that FoG is associated with either cholinopathy, amyloidopathy or both in PD. The investigators propose to test the novel hypothesis that comorbid amyloidopathy may be a possible mechanistic factor underlying the poor response of FoG to dopaminergic therapy in advancing PD. In contrast, isolated cholinopathy would be expected to be associated with preserved dopamine responsiveness of FoG. For this purpose, the investigators propose to perform detailed motor, including FoG, testing in PD patients "on" and "off" their dopaminergic medications and relate this to dopaminergic 11C-DTBZ, vesicular acetylcholine transporter 18F-FEOBV and -amyloid 11C-PIB brain PET imaging in PD subjects with and without FoG. Furthermore, based on recent clinical observations that serotoninergic drugs, like the popular anti-depressant SSRI drugs, are associated with significantly lower build- up of -amyloid plaques in the elderly population, and based on the investigators' subsequent observation of an intriguing inverse relationship between -amyloid plaque deposition and striatal serotoninergic terminal in PD, the investigators propose to perform an exploratory sub-study to test a new hypothesis that PD subjects with FoG will exhibit not only higher striatal -amyloid but also lower striatal serotoninergic innervation (as determined by 11C-DASB serotonin PET imaging) compared to PD subjects without FoG. If confirmed, positive findings in this study would allow the identification of different PD subgroups ('personalized medicine'), such as presence amyloidopathy or cholinopathy, to select patients for targeted pharmacotherapies to potentially prevent the development of FoG (anti-amyloid, such as serotoninergic drugs) or manage its clinical manifestation (cholinergic augmentation therapy) in order to preserve and maintain a good quality of life in individuals with PD.

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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Amyloidopathy, Cholinopathy, Dopamine Responsiveness and Freezing of Gait in PD
Actual Study Start Date : June 7, 2016
Estimated Primary Completion Date : June 7, 2021
Estimated Study Completion Date : June 7, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Parkinson's disease with FoG
Subjects with Parkinson's disease that have freezing of gait (FoG) who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid)
Other: Detailed motor testing, including FoG, in PD subjects
Subjects with PD with and without freezing of gait (FoG) will undergo a biomechanical assessment during a FoG provocation protocol in both the dopaminergic "on" and "off" state.

Parkinson's disease without FoG
Subjects with Parkinson's disease that do not have freezing of gait who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid)
Other: Detailed motor testing, including FoG, in PD subjects
Subjects with PD with and without freezing of gait (FoG) will undergo a biomechanical assessment during a FoG provocation protocol in both the dopaminergic "on" and "off" state.




Primary Outcome Measures :
  1. Freezing episodes during the FoG provocation protocol [ Time Frame: through study completion, up to 5 years ]
    Change in FOG episodes between "on" and "off" dopaminergic medications


Secondary Outcome Measures :
  1. Quantitative correlation of freezing episodes to brain PET imaging [ Time Frame: through study completion, up to 5 years ]
    The individual and combined effects of dopaminergic 11-C-DBTZ, vesicular acetylcholine transporter 18-F-FEOBV, and B-amyloid 11C-PIB brain PET imaging on freezing episodes.


Biospecimen Retention:   Samples With DNA
Saliva for DNA Serum (approx. 4ml)


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Community sample recruited from the following sources

  1. UMHS Movement Disorders Clinics
  2. VA Ann Arbor HS Movement Disorders Clinic
  3. Existing studies at Functional Neuroimaging, Cognitive, and Mobility Lab at the University of Michigan
Criteria

Inclusion Criteria:

  • PD based on the United Kingdom Parkinson's Disease Society Brain Bank
  • Diagnostic Research Criteria with or without Freezing of Gait
  • Duration of Disease > 5 years
  • MMSE > 23

Exclusion Criteria:

  • Dementia
  • Dementia with Lewy Bodies
  • Other disorders which may resemble PD
  • Subjects on neuroleptic, anticholinergic (trihexiphenidyl, benztropine) or cholinesterase inhibitor drugs
  • Evidence of a stroke or mass lesion on structural brain imaging (MRI)
  • Participants in whom MRI is contraindicated including, but not limited to:

    • those with a pacemaker
    • presence of metallic fragments near the eyes or spinal cord
    • cochlear implant
  • Severe claustrophobia precluding MR or PET imaging
  • Subjects limited by participation in research procedures involving ionizing radiation
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03647137


Contacts
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Contact: Chrisine Minderovic, BS (734) 883-8400 pdresearch@med.umich.edu

Locations
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United States, Michigan
VA Ann Arbor Healthcare System, Ann Arbor, MI Recruiting
Ann Arbor, Michigan, United States, 48105
Contact: Cyrus B Sarosh, BA    734-499-8400    pdresearch@med.umich.edu   
Principal Investigator: Nicolaas I Bohnen, MD PhD         
Sponsors and Collaborators
VA Office of Research and Development
University of Michigan
Investigators
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Principal Investigator: Nicolaas I Bohnen, MD PhD VA Ann Arbor Healthcare System, Ann Arbor, MI

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03647137     History of Changes
Other Study ID Numbers: B1631-I
HUM00110351 ( Other Identifier: University of Michigan )
First Posted: August 27, 2018    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
freezing of gait
amyloid
cholinergic
mobility
PET
imaging
MRI

Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dopamine
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents